By using antisera directed against specific cell surface antigens, it has been possible to identify and purify cultured rat Schwann cells. It is proposed firstly to examine their interaction in culture with dissociated dorsal root ganglion neurons which are myelinated in vivo, and secondly to examine their interaction with skeletal muscle which induces acetylcholine synthesis in the Schwann cell. A major objective is to identify that quality of certain neurons which initiate myelination by the Schwann cell. Immunological methods will be used to prepare antisera against both neurons and Schwann cells with the aim of identifying surface components that are involved in myelination. These sera will be investigated in a defined, dissociated system which allows the production of myelin proteins to be quantitated by biochemical and immunochemical assays. The induction of acetylcholine synthesis by cultured embryonic or adult muscle will be followed by measuring the level of choline acetyltransferase as well as by direct assays of acetylcholine synthesis from radioactive choline. If the interaction is mediated by soluble factors released by the muscle, an attempt will be made to characterize and investigate the molecules resonsible. The Schwann cells divide very slowly in culture but are stimulated by a protein present in extracts of the brain and pituitary. This component is an apparently novel growth factor/hormone which will be purified in order to investigate its properties and function. This experimental program would define the factors involved in inducing myelin or acetylcholine synthesis in the Schwann cell, and has implications for possible therapy of demyelinating disease by using cultured Schwann cells to repair demyelinated axons.